Potent Regulation of Midbrain Dopamine Neurons by the Bed Nucleus of the Stria Terminalis

Abstract

Recent studies have revealed an important role of the ventrolateral (subcommissural) aspect of the bed nucleus of the stria terminalis (vBNST) in motivational aspects of drug abuse (Delfs et al., 2000). Dopaminergic (DA) neurons in the ventral tegmental area (VTA) have also long been linked to motivation and drug abuse (Koob and Le Moal, 2001). The present study tested whether activity in the vBNST influences discharge of midbrain DA neurons. Responses of DA neurons in the VTA to activation of the vBNST were characterized in anesthetized rats using extracellular recording techniques. Electrical or chemical [10-50 mm glutamate (Glu)] stimulation of the vBNST consistently activated DA cells (122% increase in activity with 50 mm Glu). However, stronger chemical stimulation of the vBNST (100 mm Glu) completely inactivated DA neurons. In addition, apomorphine restored the activity of DA neurons that were inactivated by 100 mm Glu stimulation of the vBNST, indicating possible depolarization blockade of DA cells by vBNST activity. These findings reveal that the vBNST exerts a strong excitatory influence on DA neurons. Also striking was the finding that chemical stimulation (50 mm Glu) of the vBNST yielded long-lasting oscillatory activity (>15 min) in VTA DA neurons. These results indicate that the vBNST can generate long-lasting alterations in the activity of DA neurons in vivo.